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Dieckol Attenuates Microglia-mediated Neuronal Cell Death via ERK, Akt and NADPH Oxidase-mediated Pathways. | LitMetric

AI Article Synopsis

  • Excessive activation of microglia, which leads to neuroinflammation, contributes to synaptic loss and neuron death, playing a role in neurodegenerative diseases, prompting the exploration of therapeutic strategies that target microglial activation.
  • The study investigates dieckol (DEK), a compound from the brown alga Ecklonia cava, and its effects on microglial activation through specific molecular pathways, aiming to clarify its neuroprotective mechanisms.
  • Results show that DEK effectively reduces the activation of signaling pathways (ERK, Akt, and NADPH oxidase) involved in microglial function, ultimately protecting neurons from cell death caused by neurotoxic substances released by activated microglia.

Article Abstract

Excessive microglial activation and subsequent neuroinflammation lead to synaptic loss and dysfunction as well as neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases. Thus, the regulation of microglial activation has been evaluated as effective therapeutic strategies. Although dieckol (DEK), one of the phlorotannins isolated from marine brown alga Ecklonia cava, has been previously reported to inhibit microglial activation, the molecular mechanism is still unclear. Therefore, we investigated here molecular mechanism of DEK via extracellular signal-regulated kinase (ERK), Akt and nicotinamide adenine dinuclelotide phosphate (NADPH) oxidase-mediated pathways. In addition, the neuroprotective mechanism of DEK was investigated in microglia-mediated neurotoxicity models such as neuron-microglia co-culture and microglial conditioned media system. Our results demonstrated that treatment of anti-oxidant DEK potently suppressed phosphorylation of ERK in lipopolysaccharide (LPS, 1 µg/ml)-stimulated BV-2 microglia. In addition, DEK markedly attenuated Akt phosphorylation and increased expression of gp91 (phox) , which is the catalytic component of NADPH oxidase complex responsible for microglial reactive oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal cell death that is induced by treatment of microglial conditioned media containing neurotoxic secretary molecules. These neuroprotective effects of DEK were also confirmed in a neuron-microglia co-culture system using enhanced green fluorescent protein (EGFP)-transfected B35 neuroblastoma cell line. Taken together, these results suggest that DEK suppresses excessive microglial activation and microglia-mediated neuronal cell death via downregulation of ERK, Akt and NADPH oxidase-mediated pathways.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422961PMC
http://dx.doi.org/10.4196/kjpp.2015.19.3.219DOI Listing

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